Drospirenone is a synthetic progestin widely used in contraceptive therapy. Chemically known as 6β,7β,15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone, it has the following structural formula 5.

Several synthetic routes for the production of Drospirenone have been proposed so far, such as, for example, those disclosed in U.S. Pat. No. 6,121,465, WO2006/059168, WO2006/061309, U.S. Pat. No. 7,585,971B2, U.S. Pat. No. 7,319,154B2, U.S. Pat. No. 6,933,395, U.S. Pat. No. 4,416,985.
The oxidation processes reported in the prior art (WO2008/137050, U.S. Pat. No. 7,585,971B2, U.S. Pat. No. 7,319,154B2, EP075189, U.S. Pat. No. 6,933,395B1 and EP2019114A1) are performed starting from compound 3 or from a mixture of compound 3 and the epimers of lactol 8

WO2008/137050 to Sicor describes the oxidation of intermediate 3 to Drospirenone using potassium permanganate.
The preparation of Drospirenone 5 by oxidation of intermediate 3 and/or the epimeric lactols 8 using reagents such as pyridine-SO3 complex and TEMPO/calcium hypochlorite, potassium tert-butylate/cyclohexanone, manganese (IV) oxide, or N-methylmorpholine N-oxide (NMMO)/Tetrapropylammonium perruthenate (RAP) are disclosed in U.S. Pat. No. 7,585,971B2 to Industriale Chimica.
In U.S. Pat. No. 7,319,154B2 to Schering the oxidation of compound 3 to Drospirenone through the 3-oxo-lactone intermediate 4 using TEMPO/sodium hypochlorite allows to obtain Drospirenone 5 in 77% overall yield.

EP075189 to Schering discloses the oxidation of 3 to 5 using Cr(VI)O3/Pyr in 56% overall yield.
U.S. Pat. No. 6,933,395B1 to Schering discloses overall yields of 65% for the oxidation of 3 to 5 using sodium bromate as oxidizing agent in the presence of ruthenium(III) chloride.
A two-step conversion of intermediate 3 protected at the primary hydroxyl group as the trimethylsilyl derivative compound 17α-[3-(trimethylsilanyloxy)propyl]-6β,7β,15β,16β-dimethyl en-5β-androstane-3β,5,17β-triol 2a) into Drospirenone 5 using 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (2-iodoxybenzoic acid, IBX) followed by the Jones reagent is described in EP2019114A1 to Newchem. The conversion proceeds in 51% overall yield.
